Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
Int J Oncol. 2017 Aug;51(2):644-656. doi: 10.3892/ijo.2017.4047. Epub 2017 Jun 21.
Endometrial cancer (EC) is the third most common gynecologic malignancy in the world, and is considered a chemotherapy poor responding cancer. There are two underlying mechanisms on chemoresistance: the stemness of cancer stem cells (CSCs) and activation of pro-survival autophagy. It was found that autophagy is one of the main factors of cancer stem cell survival, multidrug resistance and maintenance of the homeostasis of cancer stem cells and normal cancer cells. However, the relationship between CSCs and autophagy of EC cells is still unknown. In this study, higher autophagy level was found in endometrial cancer stem cells (ECSCs) and stemness kept in line with autophagy in successive cultured JEC spheres. Autophagy inhibition decreased the properties of CSCs in JEC spheres and enhanced sensitivity of ECSCs to paclitaxel. Besides, it was found that EIG121 exerted dual functions in the regulation of autophagy and stemness not only in normal JEC cells but also JEC obtained CSCs. These findings could be useful for developing targeted therapies for endometrial carcinoma.
子宫内膜癌(EC)是世界上第三常见的妇科恶性肿瘤,被认为是一种对化疗反应不佳的癌症。有两种潜在的耐药机制:癌症干细胞(CSC)的干性和存活自噬的激活。研究发现,自噬是癌症干细胞存活、多药耐药和维持癌症干细胞和正常癌细胞内稳态的主要因素之一。然而,EC 细胞中 CSCs 和自噬之间的关系尚不清楚。在这项研究中,发现子宫内膜癌干细胞(ECSCs)中的自噬水平更高,并且在连续培养的 JEC 球体中,干性与自噬保持一致。自噬抑制降低了 JEC 球体中 CSCs 的特性,并增强了 ECSCs 对紫杉醇的敏感性。此外,还发现 EIG121 不仅在正常 JEC 细胞中,而且在获得 CSCs 的 JEC 中,对自噬和干性的调节具有双重功能。这些发现可能有助于为子宫内膜癌开发靶向治疗。